IL-34 Upregulated Th17 Production through Increased IL-6 Expression by Rheumatoid Fibroblast-Like Synoviocytes

Abstract EN

Rheumatoid arthritis (RA) is a chronic autoimmune disease which is characterized by synovial inflammation and cartilage damage for which causes articular dysfunction.

Activation of fibroblast-like synoviocytes (FLS) is a critical step that promotes disease progression.

In this study, we aimed to explore the effect of interleukin-34 (IL-34) on RA FLS as a proinflammatory factor and IL-34-stimulated FLS on the production of Th17.

We found that serum IL-34 levels were increased compared to those of the healthy controls and had positive correlations with C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), and anticyclic citrullinated peptide (CCP) antibody accordingly.

CSF-1R was also highly expressed on RA FLS.

The interaction of IL-34 and CSF-1R promoted a dramatic production of IL-6 by FLS through JNK/P38/NF-κB signaling pathway.

Further, the IL-34-stimulated IL-6 secretion by RA FLS was found to upregulate the number of Th17.

The treatment of IL-6R antagonist could attenuate the production of Th17 mediated by IL-34-stimulated RA FLS.

Our results suggest that the increased IL-34 levels were closely related to the disease activity of RA.

Additionally, the overexpression of IL-6 in the IL-34-stimulated FLS promoted the generation of Th17.

Therefore, IL-34 was supposed to be involved in the pathogenesis of RA.

The inhibition of IL-34 might provide a novel target for therapies of RA.